Drugs and the pharmaceutical sciences

728 Cole
from 165˚C (329˚F) and exhibit considerable softening at typical sterilizing temperatures.
A disposable filter element, while usually robust at normal room temperatures, can be
easily crushed using a (gloved) hand when heated to 121˚C (250˚F) or above. Disposable
filter assemblies (capsules) can suffer damage as a result of deformation of the plastic
materials during autoclaving.
1. An object resting against or placed on top of a filter capsule may be sufficiently
heavy to deform the capsule during the cycle, thus making the capsule no longer
safe to use under pressure or perhaps changing the capsule’s shape so that it no
longer fits correctly in its normal operating position. Attention to procedures for
autoclave loading will prevent this problem.
2. Plastic filter capsules are commonly attached to stainless steel vessels by means of
sanitary tri-clamp connections. One side of the connection (from the vessel) will
usually be stainless steel while the other connection (the filter capsule) is plastic
(typically polypropylene). The joint is secured with a stainless steel tri-clamp and
an elastomeric gasket. During steam sterilization, differential expansion of the two
flange materials and the gasket leads to distortion of the plastic flange on the filter
connection, so that it no longer seals correctly. The effect is often exacerbated by a
tendency to overtighten the clamps and is also exaggerated by the great disparity in
heat capacity of the two flange materials; the steel components remain hot for a
long time after the plastic filter materials have cooled. Use of the strong plastic triclamps
currently available will eliminate most of the steel mass in this situation;
alternative plastic connections to the vessel should be considered, for example,
PTFE or polypropylene.
It is important to consider the sizing and duty of small disposable hydrophobic filter
assemblies used as vents on equipment assemblies during both autoclave sterilization and
normal operation. The sizing affects not only the likelihood of damage being caused to
the filter but also the risk of damaging or destroying the equipment assembly itself. The
following examples illustrate important considerations:
3. Small portable steel receiving vessels for sterile product are sterilized by
autoclaving; a vacuum-cycle is employed before and after the sterilization period,
to aid steam penetration and post-cycle drying. A small hydrophobic vent filter
capsule (with a membrane area of approximately 500 cm 2 ) is used to enable venting
during filling of the vessel and pressurization to empty it. The filter capsule is
secured to the top plate of the vessel by means of a short length of flexible silicone
hose that joins hose-tail connectors on the top plate and the filter outlet. The inlet to
the filter capsule does not need to be wrapped, because the filter membrane protects
the interior of the system from airborne contamination after sterilization. When the
equipment is ready to be sterilized, the entire assembly is placed into a large
autoclave chamber; the silicone tubing is sufficiently strong to support the weight
of the dry filter capsule in an upright position. A test of filter integrity performed
after use of the equipment revealed that the filter membrane was damaged and
examination showed the filter had experienced an excessive differential pressure at
elevated temperature in the reverse flow direction.
At the temperature of the autoclave sterilization cycle the silicone tubing had
softened. At the same time some steam had condensed in the filter capsule in the
early stages of the cycle. The combined effects of increased filter weight and
softening of the tubing caused the filter to collapse from its upright position; the
end result was occlusion of the tubing where it became kinked between the filter